iBB

The Blue Bioeconomy Pact led by Inovamar is one of the mobilizing agendas for corporate innovation recently funded by the European Union NextGenerationEU through the Portuguese Recovery and Resilience Plan (PRR). It consists of a consortium of 83 national entities including 53 companies of all dimensions, from large multinational corporations to small-medium enterprises and start-ups, and 30 R&D institutions. The project aims to develop the sustainable use of marine resources, creating 52 new products, processes and services across multiple sectors such as aquaculture, fisheries, food and feed, textiles, biomaterials and human health. The consortium will invest a total amount of 133 M€, of which 94 M€ are financed by the Recovery and Resilience Plan.

Instituto Superior Técnico is involved in four of the nine PBA work packages with 1.5 M€ of funding: WP1 – “Biomaterials”, WP4 – “Food”, WP5 – “Algae”, and WP9 – “The Portuguese Blue Biobank”. The project at IST is coordinated by Prof Rodrigo Costa from iBB and DBE and counts on expert contributions by Dr Teresa Cesário from iBB (WP1), Dr Tina Keller-Costa and Prof Isabel Sá-Correia from iBB (WP5 and WP9) and Prof Ana Clara Marques from CERENA and DEQ (WP4).

Gold(III) bisdithiolate complexes have been shown as potential antimicrobial and antitumoral agents. In particular, the complex [Au(cdc)2]− (cdc=cyanodithioimido carbonate) displayed antimicrobial and outstanding antitumor activity against the ovarian cancer cells A2780 and A2780cisR, which are sensitive and resistant to cisplatin, respectively. Yet, poor water solubility may hinder its clinical use. Block copolymer micelles (BCMs) have demonstrated great potential as nanocarriers capable of delivering hydrophobic drugs, increasing their solubility and stability, and improving their bioavailability and circulation time in blood, with reduced side effects. In this work, published in the journal Pharmaceutics, the potential of BCM-[Au(cdc)2] as a novel drug-delivery system was addressed. The BCM-[Au(cdc)2] micelles were prepared with a loading efficiency of 64.6% and a loading content of 35.3 mg [Au(cdc)2]−/gBCM, they were also homogenous and good candidates for drug delivery. Cytotoxic activity studies against A2780/A2780cisR cells showed that BCM-[Au(cdc)2] maintained relevant cytotoxic activity comparable to the cytotoxicity observed for the same concentration of gold complexes. The Au uptake in A2780 cells, determined by PIXE, was ca. 17% higher for BCMs-[Au(cdc)2] compared to [Au(cdc)2]−. The BCMs-[Au(cdc)2] presented also antimicrobial activity against S. aureus Newman and C. glabrata CBS138. In summary this paper shows the results of the potential of BCM-[Au(cdc)2] for drug delivery and its promising anticancer and antimicrobial activities.

This study was led by Dr. Célia Fernandes and Dr. Fernanda Marques, both from Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico. The iBB members Teresa Pinheiro, Jorge Leitão and Sílvia Sousa collaborated in this work performing the cellular uptake analysis and the antimicrobial activities of BCMs.

The Academic Jubilee of Isabel Sá-Correia, Distinguished Professor at the Departamento de Bioengenharia (DBE) and researcher at the iBB - Institute for Bioengineering and Biosciences will take place on the 7th February, at 5 p.m., in Instituto Superior Técnico congress centre.

Programme:
5 p.m. – Opening session – João Pedro Conde – Head of DBE
5.05 p.m. – Rogério Colaço – President of Técnico
5.10 p.m. – Jorge Pedrosa – Presidente da Sociedade Portuguesa de Microbiologia
5.15 p.m. – Joaquim Cabral – DBE
5.20 p.m. – Arsénio Fialho – DBE
5.25 p.m. – Jorge Leitão – DBE
5.30 p.m. – Isabel Sá-Correia – 30 min “As Ciências Biológicas numa Escola de Engenharia” (“Biological Sciences in a School of Engineering”)
6 p.m. – Luís Ferreira – Rector of Universidade de Lisboa
6.05 p.m. – Closing session and "Porto de Honra"

Metagenomics is an expanding field within microbiology and related disciplines. The number of metagenomes deposited in public databases is exponentially rising, but data mining and interpretation can be challenging due to mis-annotated metadata entries. The new Marine Metagenome Metadata Database (MarineMetagenomeDB) helps researchers to identify marine metagenomes of interest for re-analysis and meta-analysis and is a valuable resource for non-bioinformaticians to find marine metagenome samples with curated metadata. The study, published in Environmental Microbiome, was led by Dr Ulisses Nunes da Rocha and team from the Helmholtz Centre for Environmental Research (Germany), and counted on specialist guidance in marine metadata standardization from iBB/DBE PhD-student Sandra Silva and researchers Tina Keller-Costa and Rodrigo Costa. The user-friendly web app is publicly available at here.

Mónica Galocha was distinguished with the Best PhD Work in Research and Infectious Diseases by redeSAÚDE, University of Lisbon, at the 6th redeSAÚDE conference held at University of Lisboa on the 15th of November 2022. Mónica Galocha presented her research focused on unveiling new pathways of genomic evolution towards drug resistance in Candida glabrata, carried at iBB, under the supervision of Professor Miguel Cacho Teixeira.

Genome sequencing is a powerful tool that contributes to the advancement of drug resistance studies, population dynamics and evolution in fungal pathogens. In a paper just published in Microbial Cell, emerging from a collaboration between Miguel Cacho Teixeira’s team, iBB, and Hiroji Chibana, MMRC, Japan, the analysis of nearly 100 genomes of globally distributed C. glabrata isolates enabled the identification of new effectors of azole and echinocandin resistance. Their genomic landscape was further explored to evaluate genetic variants specific to each drug resistance profile. Interestingly, the data concludes that changes in the most studied drug resistance genes only occur in a fraction of the resistant isolates, an observation that is expected to contribute to design more suitable antifungal therapeutic strategies.

Protein kinases are essential as signal transductors for a proper cellular response to extracellular stimuli. A BSRG-iBB review paper, just published in Computational and Structural Biotechnology Journal gathers the available information regarding the NPR/Hal5 family of kinases in Saccharomyces cerevisiae and non-Saccharomyces species of clinical and biotechnological relevance. These kinases - for which information is scarce and scattered across scientific literature - are essential modulators of yeast nutrient availability responses and ion homeostasis. This publication has as first-author the PhD student Miguel Antunes of the IST PhD programme in Biotechnology and Biosciences and the FCT-DP BIOTECnico - and as a corresponding author his thesis supervisor, Professor Isabel Sá-Correia.

In a perspective article published in Nature Microbiology, experts in the field of symbiosis and microbiome research address the current, acute loss of plant and animal diversity that poses serious threats to the functioning of terrestrial and marine ecosystems, human health, and the development of a sustainable bio-based economy. The potential, and examples of success, of microbiome-based interventions such as probiotics administration and microbiome transplants in improving the health and resilience of a broad range of host organisms towards climate change stressors and the emergence of novel diseases is debated, and a perspective is provided on how such interventions may contribute to the conservation and maintenance of services of man-made and natural ecosystems. The perspective, led by Prof. Raquel Peixoto at King Abdullah University of Science and Technology (KAUST), counted on expert contributions by iBB-BSRG researchers Dr. Rodrigo Costa and Dr. Tina Keller-Costa on microbiome manipulation strategies in aquaculture and coral reef ecosystems. The initiative was launched by a round table headed by the Beneficial Microorganisms for Marine Organisms (BMMO) network during the 15th Symposium on Bacterial Genetics and Ecology (BAGECO15, Lisbon 2019) chaired by Prof. Rodrigo Costa.

Bacterial pathogens belonging to the Vibrio genus such as Vibrio parahaemolyticus, Vibrio alginolyticus and Vibrio vulnificus are some of the most common and widespread disease-causing agents in the aquaculture industry, inducing severe losses in fish and shellfish production worldwide. In a Review Article published in Frontiers in Microbiology, iBB researchers Gracinda Sanches Fernandes, Isabel-Sá Correia and Rodrigo Costa performed a meta-analysis of vibriosis outbreaks reported for the economically valuable, model aquaculture fish gilthead seabream (Sparus aurata) in the Mediterranean zone. The study reveals the acquisition of multiple antibiotic resistance traits among pathogenic Vibrio species during the past 25 years. An increase in human infections caused by Vibrio pathogens of fish – either via seafood ingestion or wound colonization - has been documented in the recent literature, and it is believed to result from the synergistic interaction between the expansion of intensive fish farming across coastal ecosystems and global warming. Finally, the authors critically examine the potential, and review cases of success, of alternative methods to antibiotics use to suppress vibrio pathogens in aquaculture, including vaccines, phage therapy and probiotics supplementation. Diverse bacterial symbionts of fish suppress vibrio pathogens in experimental trials, suggesting that the natural fish microbiome may be a reservoir of biological control agents of interest in applied biotechnology.

Sandra Godinho Silva, PhD candidate in Biotechnology and Biosciences, presented a talk entitled 'Big data meets natural products discovery: mining thousands of bacterial genomes to identify novel sources of drug leads' at the FEMS Conference on Microbiology 2022, held from 30 June to 2 July 2022 in Belgrade, Serbia. Her presentation explored the results of a large-scale comparative genomics approach to study natural product biosynthesis potential across 2680 bacterial genomes representing 1158 species and 175 genera of the metabolically-versatile order Flavobacteriales (phylum Bacteroidetes). Sandra was awarded a FEMS Research and Training Grant (GO-2019-511) to conduct her studies in the framework of an international collaboration on high-throughput genome mining led by Prof. Rodrigo Costa (BSRG-iBB, Portugal) and Dr. Ulisses N. da Rocha (Microbial Data Science Group, Helmholtz Centre for Environmental Research - UFZ , Leipzig, Germany). The results will be compiled in Sandra’s PhD thesis, under the supervision of Prof. Rodrigo Costa and Dr. Tina Keller Costa (BSRG-iBB). Sandra also had the opportunity to co-chair an oral poster session with Prof. Bauke Oudega on 'FEMS Supported Projects & Miscellaneous', and her participation in the FEMS 2022 Conference was supported by a FEMS Congress Attendance Grant.

A new study provides insights into the prokaryotic communities and heavy metal distribution in different body parts of the marine sponge Chondrosia reniformis, a model organism relevant for marine conservation and biotechnology. The study was published in Zoology and results from an international collaboration between researchers from iBB-IST and the Università Politecnica delle Marche in Italy.  The work was led by Italian PhD student Camilla Roveta and Prof. Rodrigo Costa from BSRG-iBB/DBE and included MIT Portugal PhD student Joana F. Couceiro from BSRG-iBB. Fifteen prokaryotic phyla were detected in association with this sponge. Three lineages of ammonium-oxidizing organisms co-dominated the prokaryotic community, suggesting ammonium oxidation/nitrification as key metabolic pathway within the C. reniformis microbiome. Mercury levels varied according to the body site of the sponge, with higher levels accumulating in internal sites (choanosome). Minor levels of Hg could be detected in the microbial fractions extracted from the sponge host, suggesting that the sponge-associated microbiome may participate in Hg adsorption and removal processes in benthic ecosystems. This study paves the way for scientists to deepen the possible application of marine sponges not only as bioindicators of environmental health, but also as bioremediation tools of metal polluted environments.

Mónica da Luz Galocha defended her PhD thesis in Biotechnology and Biosciences, titled “Unveiling new pathways of genomic evolution towards drug resistance in Candida glabrata”, on the 13th of February 2023, at Instituto Superior Técnico. During the previous four years, and under the supervision of Miguel Cacho Teixeira from iBB, Mónica studied the genomic basis of the evolution towards antifungal drug resistance in the fungal pathogen Candida glabrata, uncovering fascinating new mechanisms of azole drug import and transcriptome-wide remodelling in the dependency of mediator complex components.

A new article provides a genome-based roadmap to facilitate the selection of coral probiotics, also known as Beneficial Microbes for Corals (BMCs), and was just published in mSystems. Probiotics are starting to be investigated as a potential medicine for corals, marine animals that are threatened with extinction by the advance of climate change. Laboratory experiments have already proved the concept that coral probiotics mitigate coral bleaching and reduce coral mortality. This study now employed comparative genomics to identify exclusive BMC traits associated with specific probiotic strains and proposed new BMC mechanisms. The work was led by Prof Raquel Peixoto and her team from KAUST University at the Red Sea and received guidance on genomics of coral-associated bacteria from iBB/DBE researcher Dr Tina Keller-Costa.

Marine microbiomes are prolific sources of bioactive compounds of pharmaceutical value. A new study, published in Marine Drugs, inspected two culture collections comprising 919 host-associated marine bacteria belonging to 55 genera and several unclassified lineages. The study identified numerous isolates with a potentially rich secondary metabolism and inhibitory activities towards human-pathogenic bacteria and fungi. These culture collections, available at iBB-IST and Aveiro University, are a valuable resource of understudied marine bacteria that hold promise for a future, sustainable production of novel drug leads. The work was developed within the SymbioReactor project (DGPM | Fundo Azul program), first-authored by MSc João Almeida and coordinated by Dr Tina Keller-Costa and Prof Rodrigo Costa. The study also involved PhD student Matilde Marques, Dr Dalila Mil-Homens, Prof Miguel Teixeira and Prof Arsénio Fialho from iBB as well collaborators from Aveiro University and Biocant.

The video of a recent conference on the “Funding of Science”, included in the Cycle of Conferences – Challenges of Science in Contemporary Society, was published on the YouTube of Academia de Ciências de Lisboa. The session was chaired by Professor Isabel Sá-Correia from iBB - Institute for Bioengineering and Biosciences . This theme touches deeply the scientific community. Undoubtedly, the scientific and technological development of a country, an institution, a research group requires, in addition to adequate and coherent policies, very costly investments, very significant and continuous funding. But, even if the funding of science is obviously critical, this is not limited to the funds that are made available, to the % of the Gross domestic product (GDP) that governments and private institutions dedicate to research and there is a lot of material for reflection.
The cycle of conferences dedicated to Science challenges in contemporary society is promoted by the Instituto de Alto Estudos of ACL. 

The YEASTRACT+ information system is a wide-scope computational tool for the analysis and prediction of transcription regulatory associations at the gene and genomic levels in 11 yeast species of biotechnological or human health relevance. Its newest release, orchestrated by a large team led by Isabel Sá-Correia, Miguel Teixeira, from iBB, and Pedro Monteiro, from INESC-ID, has just described in the 2023 Nucleic Acids Research Database Issue, highlighting the availability of new regulatory-metabolic network modeling tools. These tools are expected to contribute to guide YEASTRACT+ users in the optimization of yeast cell factories of industrial relevance and the identification of new antifungal drug targets, to be used in advanced antifungal therapy. YEASTRACT+ is currently supported within the context of the Biodata.pt/Elixir.pt Research Infrastructure.

Following the genomic alterations occurring in a cell population as it evolves towards drug resistance in C. glabrata is a promising way of identifying the drug resistance mechanisms that actually take place in the clinical setting. In a recent study, lead by Miguel Cacho Teixeira’s (BSRG-iBB) and Acácio Rodrigues’ (CINTESIS-FMUP) teams, together with Patrick Van Dijck (UCL, Louvain, Belgium), Hiroji Chibana (MMRC, Chiba Univ, Japan) and Cláudio Soares (ITQB-NOVA), the genomic changes underlying Posaconazole resistance acquisition in C. glabrata were evaluated. Based on the obtained results, the hexose transporters Hxt4/6/7 and Hxt6/7 were identified and determinants of azole susceptibility and proposed to act as azole importers. These results, recently published in Communications Biology, are believed to be just the tip of the iceberg, as many other hexose transporter family members may play similar roles in all fungal pathogens.

To shed light on the metabolic capacities of the bacterial symbionts of octocorals (Octocoallia, Cnidaria), iBB researchers examined 66 metagenome-assembled genomes (MAGs) from the microbial metagenomes of octocorals and seawater. The work recovered MAGs from dominant, so-far unculturable Endozoicomonadaceae and other symbionts, and identified a thus far unanticipated, global role for Endozoicomonadaceae symbionts of corals in the processing of chitin, the most abundant natural polysaccharide in the ocean. Other symbionts had genes for the assimilation of chitin oligosaccharides and for chitin deacetylation, suggesting possibilities for substrate cross-feeding and a role for the coral microbiome in overall chitin turnover. The study also observed sharp differences in secondary metabolite production potential between symbiotic lineages, and suggested that niche partitioning, metabolic specialization, and adaptation to low oxygen conditions among prokaryotic symbionts likely contribute to the plasticity and adaptability of the octocoral holobiont in changing marine environments. The article, published in the journal Microbiome, was led by iBB researchers Tina Keller-Costa and Rodrigo Costa and counted on contributions of EPFL MSc student Lydia Kozma, iBB PhD student Sandra Silva and collaborators from UALG-CCMAR, UFZ Leipzig and DOE JGI.

Adaptation and tolerance to industrially relevant stress factors involve highly complex and coordinated molecular mechanisms occurring in the yeast cell with repercussions on the performance and economy of bioprocesses. The cell wall is among the players whose biochemical and biophysical properties can be finely tuned as yeast cells encounter different stresses throughout the course of industrial bioprocesses. A new review article from BSRG-iBB provides a critical opinion and a comprehensive view on the current knowledge on the involvement of the cell wall in the adaptive response and tolerance of yeasts to multiple stresses of biotechnological relevance. A few successful attempts to improve stress tolerance through the manipulation of cell wall biosynthetic pathway are also described and the available information for some non-conventional yeast species included. The review article is co-authored by the PhD student of the IST PhD programme in Biotechnology and Biosciences Ricardo Ribeiro and the thesis supervisor, Prof. Isabel Sá-Correia. It was was published in the journal Frontiers in Microbiology (section: Microbial Physiology and Metabolism).

Exploration of yeast diversity for the sustainable production of biofuels, in particular biodiesel, is gaining momentum in recent years. A BSRG-iBB review paper, just published in the Journal of Fungi (Special Issue: Yeasts for a Sustainable Circular Bio-Based Economy), provides an overview of lipid production by oleaginous yeasts focusing on yeast diversity, metabolism, and other microbiological issues related to the toxicity and tolerance to multiple challenging stresses limiting bioprocess performance. Examples gathered from the literature showing the potential of different oleaginous yeasts/process conditions to produce oils for biodiesel from agro-forestry and industrial organic residues are also provided. This publication has as first-author the PhD student Marta N. Mota of the IST PhD programme in Biotechnology and Biosciences and as corresponding author her thesis supervisor, Professor Isabel Sá-Correia. Paula Múgica, from BIOREF—Collaborative Laboratory for Biorefineries, also contributed to the publication during her stay at BSRG-iBB for scientific training and collaboration in the execution of the Move2LowC project.

Dr Tina Keller-Costa, BSRG-iBB researcher, and Matilde Marques, MIT Portugal PhD student in Biotechnology and Biosciences, attended the International Coral Reef Symposium (ICRS), held from 03 to 08 July 2022 in Bremen, Germany. Tina gave a talk on her latest metagenomics studies on the octocoral microbiome while Matilde presented a poster on viruses and bacteriophage communities of octocorals and seawater. The event was hosted by the University of Bremen and counted with 1050 in-person and over 270 virtual participants. To enable a science-to-policy dialogue the symposium also welcomed leading German and international politicians, as well Prince Albert II of Monaco and H.H. Princess Mashael Saud AlShalan from Saudi Arabia, who advocated for ocean conservation and sustainability. It was the first time in its 50-years history that ICRS was brought to Europe and the first carbon neutral ICRS.

The marine bacterial genus Aquimarina is a promising source of novel natural products. A new study published in Marine Drugs demonstrated widespread ability of Aquimarina species to inhibit growth of human-pathogenic microbes such as Candida glabrata and methicillin-resistant Staphylococcus aureus, as well as Vibrio and other marine bacteria relevant to aquaculture. Metabolomics and genomics analyses of Aquimarina strains indicated the presence of novel polyketides and peptides, including cyclic depsipeptide-related compounds. The study further showed that Aquimarina species possess low-abundance distributions across marine biotopes worldwide. It emphasizes the relevance of this member of the microbial rare biosphere as a promising source of novel natural products, supporting future efforts to isolate new bioactive compounds from Aquimarina. The work was developed within the SymbioReactor project (DGPM | Fundo Azul program) led by Prof Rodrigo Costa and Dr Tina Keller-Costa and was first-authored by PhD student Sandra Silva. It also includes former MSc student Patrícia Paula, Dr Dalila Mil-Homens, Prof Miguel Teixeira and Prof Arsénio Fialho from BSRG-iBB as coauthors.